Lung cancer is largely a disease of modern man and was considered quite rare before 1900, with fewer than 400 cases described in the medical literature. However, by the mid-twentieth century lung cancer had become epidemic and firmly established as the leading cause of cancer-related death in North America and Europe, killing more than three times as many men as prostate cancer and nearly twice as many women as breast cancer. This fact is particularly distressing since lung cancer is one of the most preventable of all of the common malignancies. Tobacco consumption is the primary cause of lung cancer, a fact firmly established in the mid-twentieth century and codified with the release of the U.S. Surgeon General's 1964 report on the health effects of tobacco smoking. Following the report, cigarette use started to decline in North America and parts of Europe, and with it so did the incidence of lung cancer. To date, the decline in lung cancer is seen most clearly in men; only recently has the decline become apparent among women in the United States. Unfortunately, in many parts of the world, especially in countries with developing economies, cigarette use continues to increase, and along with it, the incidence of lung cancers is also rising. While tobacco smoking remains the primary cause of lung cancer worldwide, more than 60% of new lung cancers occur in never smokers (smoked <100 cigarettes per lifetime) or former smokers (smoked ≥100 cigarettes per lifetime, quit ≥1 year), many of whom quit decades ago. Moreover, 1 in 5 women and 1 in 12 men diagnosed with lung cancer have never smoked. Given the magnitude of the problem, it is incumbent that every internist has a broad knowledge of lung cancer and its management.
Lung cancer is the most common cause of cancer death among American men and women. More than 220,000 individuals will be diagnosed with lung cancer in the United States in 2010. The incidence of lung cancer peaked among men in the late 1980s and has plateaued in women. Lung cancer is rare below age 40, with rates increasing until age 80, after which the rate tapers off. The projected lifetime probability of developing lung cancer is estimated to be approximately 8% among males and approximately 6% among females. The incidence of lung cancer varies by racial and ethnic group, with the highest age-adjusted incidence rates among African Americans. The excess in age-adjusted rates among African Americans occurs only among men, but age-specific rates show that below age 50 mortality from lung cancer is more than 25% higher among African American than Caucasian women. Incidence and mortality rates among Hispanic and Native and Asian Americans are approximately 40–50% those of whites.
While the large majority (80–90%) of lung cancers is caused by cigarette smoking, several other factors have been implicated, although none to the extent of tobacco. Cigarette smokers have a tenfold or greater increase in risk of this cancer compared to those who have never smoked. A deep sequencing study suggested that one genetic mutation is induced for every 15 cigarettes smoked. The risk of lung cancer is lower among persons who quit smoking than among those who continue smoking; former smokers have a ninefold increased risk of developing lung cancer compared to men who have never smoked versus the twentyfold excess in those who continue to smoke. The size of the risk reduction increases with the length of time the person has quit smoking, although generally even long-term former smokers have higher risks of lung cancer than those who never smoked. Cigarette smoking increases the risk of all the major lung cancer cell types. Environmental tobacco smoke (ETS) or secondhand smoke is also an established cause of lung cancer. The risk from ETS is less than from active smoking, with a 20–30% increase in lung cancer observed among never smokers married for many years to smokers, in comparison to the 2000% increase among continuing active smokers.
While cigarette smoking is the dominant cause of lung cancer, several other risk factors have been identified, including occupational exposures to asbestos, arsenic, bischloromethyl ether, hexavalent chromium, mustard gas, nickel (as in certain nickel-refining processes), and polycyclic aromatic hydrocarbons. Occupational studies also have provided insight into possible mechanisms of lung cancer induction. For example, the risk of lung cancer among asbestos-exposed workers is increased primarily among those with underlying asbestosis, raising the possibility that the scarring and inflammation produced by this fibrotic nonmalignant lung disease may in many cases (though likely not in all) be the trigger for asbestos-induced lung cancer. Several other occupational exposures have been associated with increased rates of lung cancer, but the causal nature of the association is not as clear.
The risk of lung cancer appears higher among individuals with low fruit and vegetable intake during adulthood. This observation led to hypotheses that specific nutrients, in particular retinoids and carotenoids, might have chemopreventive effects for lung cancer. However, randomized trials failed to validate this hypothesis. In fact, studies found the incidence of lung cancer was increased among smokers with supplementation. Ionizing radiation is also an established lung carcinogen, most convincingly demonstrated from studies showing increased rates of lung cancer among survivors of the atom bombs dropped on Hiroshima and Nagasaki and large excesses among workers exposed to alpha irradiation from radon in underground uranium mining. Prolonged exposure to low-level radon in homes might impart a risk of lung cancer equal or greater than that of ETS. Prior lung diseases such as chronic bronchitis, emphysema, and tuberculosis have been linked to increased risks of lung cancer as well.
Given the undeniable link between cigarette smoking and lung cancer (not even addressing other tobacco-related illnesses), physicians must promote tobacco abstinence. Physicians also must help their patients who smoke to stop smoking. Smoking cessation, even well into middle age, can minimize an individual's subsequent risk of lung cancer. Stopping tobacco use before middle age avoids more than 90% of the lung cancer risk attributable to tobacco. However, little health benefit is derived from just "cutting back." Importantly, smoking cessation can even be beneficial in individuals with an established diagnosis of lung cancer, as it is associated with ...